Month: September 2012

Release Mitt Romney’s Genome!

by

Sociologists say we live in an age of “biological citizenship,” in which our genetic ties are as important as our political ones, and in which communities bound by disease, disability, or allergy can be more close-knit than geographical neighborhoods. In this political season, then, we cannot afford to be ignorant about the biological status of our presidential candidates.

With this in mind, I issue a call for the Romney campaign to release their candidate’s genome sequence. Four years ago, conservatives sought the release of Barack Obama’s birth certificate. Widely perceived by the left as a scam to distract attention from the issues, the tactic nevertheless reflected the right’s alertness to biology as an important factor in fitness for office. They were fighting the wrong battle–the claim was not even 47% true–but genotopia takes the point about biology and politics. We need to know Mr. Romney’s genetic status if he is to be considered for the highest office in the land, that of Tax-Cutter-in-Chief.

As a Mormon, Mr. Romney’s genealogical relationships will surely be thoroughly documented in the Family History Library in Salt Lake City. They will reveal many relevant facts about his biological status. For example, his inbreeding coefficient must, as stipulated by a little-known paragraph in the Republican platform, must be at least 0.75 (where 1.0 means you married your clone). Circumstantial evidence is not sufficient when the stakes are this high—we need to see the data.

Modern genome sequencing can also disclose many genetic conditions that could render one unfit for office:

  • In 2008, both embarrassment and campaign donations could have been spared had John McCain’s predisposition to dementia been identified.
  • A late-onset form of dementia known as Reagan’s disease has been shown to arise in the third year of the Presidential term, in afflicted individuals.
  • Ford’s ataxia, a loss of muscular control in the limbs and neck, leads to lack of coordination and often results in injury, often serious but always comical. Most often seen in former athletes who become politicians, it is inherited as a predisposition that is then made patent through lifestyle choices.
  • Genome-wide association studies have also shown high probabilization of destitution in the grammaticalness thingy of the brain—a condition known as Bushism—that could be devastating for the Decider.
  • Recently, single nucleotide polymorphisms (SNPs, or “snips”) have also been identified that show strong (well, okay, weak—but some, definitely some) correlation with proposed genes for politophobia (morbid fear of government) and aeronautaphasia, the inability to grasp aerodynamics.
  • Multiple Spousal Cadillac Syndrome—once thought relatively benign—has now been decisively linked to the tragic and devastating psychiatric condition hyperpecuniphilia, an obsessive-compulsive disorder that in late stages can lead to the afflicted sitting amid giant piles of cash, running coins through his fingers and crying out, “Mine, ha ha! All mine!”

The only way these and countless other politicogenetic disasters can be decisively avoided is by getting Mr. Romney to step up to the plate and spit into the cup. Indeed, the Romney campaign should be anxious to prove their candidate’s biological fitness. A quick-and-dirty genome profile can be had for a few hundred dollars, and a gold-plated whole genome analysis for a few thousand. We should demand that Mr. Romney produce his entire sequence for public scrutiny and haplotype analysis. Remember: should he win in November, Paul Ryan would be just a SNP away from the Oval Office.

Decoding ENCODE

by

When I was a science writer at Cold Spring Harbor Laboratory, back in the early 1990s, I attended the annual genome meeting and heard Sydney Brenner make his pitch for the fugu genome. The puffer fish—known to sushi aficionados and neurobiologists for its tiny gland that produces the neurotoxin tetrodotoxin—Brenner, said, has a marvelously condensed genome, free of “junk DNA.”

The standard dogma of the day was that the human genome was 99% junk—an evolutionary midden-heap, strewn with the discarded wrecks of past experiments, genes that had mutated out of all functionality, mind-numbing repetitive sequences where the polymerase got stuck and churned out the nucleotide version of Nebraska, and spare parts that might be used in assembling some future genetic component. The Human Genome Project would take far longer and be far more expensive if we tried to sequence all of it, Brenner said. By studying the fugu genome, he argued, we could cut to the chase, learning about the genes without sifting through all this trash; perhaps then we could use fugu genes to identify the functional sequences in the human genome. But Brenner’s Fugu Genome Project went into science’s own scrapheap. Not long after this meeting, Craig Venter’s shotgun sequencing techniques began to accelerate the Human Genome Project, shortening the projected finish time and slashing budget projections. The Fugu Genome Project continued, but it had nothing like the impact Brenner envisioned.

Barbara McClintock, from CSHL Archives

Then I went back to grad school, studied the history of science, and began my dissertation research on Barbara McClintock, the maize geneticist who worked at Cold Spring Harbor for half a century and who won a Nobel prize in 1983 for her discovery of mobile genetic elements. Late in her career, McClintock became deeply interested in all forms of gene regulation. Development and evolution were united in her mind by means, dimly understood, of turning genes on and off and modulating their activity. She was convinced there was a higher-order organization that controlled the genes; phenotypes resulted from patterns of gene action. Most people think that McClintock’s discovery of transposable elements was ignored or dismissed by the scientific community. I found that wasn’t true. They believed that McClintock had found movable elements. They just didn’t believe those elements controlled evolution. McClintock’s late work continued her theme of gene regulation and interaction. The genome, she wrote, was a “sensitive organ of the cell,” dynamic and responsive—not a blueprint or an instruction manual.

Study of the human and other genomes has revealed that “junk DNA” is itself junk—much of that noncoding sequence is involved in gene regulation. Some of it is of the sort that McClintock envisioned; some is beyond even her imagination. The genome is now understood in terms much closer to McClintock’s mystical-sounding notion. As I wrote in my book, The Tangled Field, she deserves more credit as an early proponent of the complex, dynamic genome.

This week, the genome community has been all aflutter with news of the ENCODE project, a sophisticated genome database that catalogs patterns of gene activity. It turns out that most of Brenner’s junk DNA, isn’t. Much of that non-gene sequence is deeply important to gene function: it’s full of regulatory sequences, what the press are calling “switches,” that determine how and when and in what context the genes act. Had the National Institutes of Health invested as heavily in fugu as Brenner had hoped, it would likely have taken much longer to reach this level of subtle understanding. As Michael Eisen points out in a nice critique of the science media machine, none of this is actually news. The junk DNA model has been out of style in science for years, and the ENCODE project has not identified “millions of switches” that regulate the genome. More accurate to say, it has identified millions of potential switches—all the science of those switches still has to be done. Many of the science writers who have plumped this story simply dressed up the ENCODE project’s press release, dumbing down a lot of complex science into an easily digestible but historically misleading narrative.

Oversimplification is endemic in both science and science journalism. The former is a set of methods for making the complex simple—and the latter is a set of methods for making science simple. I did both before studying history, which is a set of methods for making the simple complex—or, rather, for decoding the complexity in what we oversimplify. Addressing subjects as massively complex and integrated as the genome—or the brain, or the immune system, or an ecological community—requires both approaches.